The objective of the project is to develop a digital specimen tomosynthesis (DST) system, based upon the clinical specimen radiography (SR) system for performing rapid, volumetric imaging of breast lumpectomy specimen in or near a surgical suite. Even though SR is used currently for surgical positive-margin evaluation, pathological examination guidance, and other clinical/preclinical applications, its utility is limied by the lack of volumetric information about specimens in SR images. The proposed DST can yield useful volumetric information about the specimen by virtue of which overlapping anatomic structures can be discerned, yet involving only minimal modifications to clinical SR. It can accomplish the imaging task within 1-2 minutes, an acceptable clinical time for a rapid evaluation of the specimen in identifying positive margins in and near an operating suite, thus reducing the frequency of positive margins being identified, and of consequent re- excisions, post surgically. It can also be used for improving accuracy in pathologic examinations by providing guidance to the pathologist to focus on regions in the specimen with the highest probability of positivity, thus increasing the sensitivity of the pathology process by reducing the incidence of missed positive regions due to suboptimal sampling. Because multiple SR images, including the ones used in current clinic evaluation, are collected in DST imaging, the DST thus retains the full functionality of current SR, and would not alter the workflow in the operating room, but only enhance the quality of information obtained from imaging, leading to improved decision making. Because the DST is designed based upon an inexpensive SR system that is used widely in breast-surgery suites, it provides an economical, practical solution which can readily be disseminated. Knowledge gained in the project can be exploited for the design and development of advanced, application- specific emerging X-ray-based tomographic imaging systems in image-guided surgery and radiation therapy, and in extremity imaging. The specific aims of the project are (1) to develop DST for rapid, volumetric imaging of lumpectomy specimen; (2) to develop algorithms for enabling DST imaging of lumpectomy specimen; and (3) to evaluate the performance of DST-scan configurations/algorithms.